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Purpose The primary aim of this study was to compare the effectiveness of oral uracil-tegafur (UFT) with that of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) given as postoperative adjuvant treatment to women with node-negative, high-risk breast cancer. Patients and Methods Women with node-negative, high-risk breast cancer were randomly assigned to receive either 2 years of UFT or six cycles of CMF after surgery. The primary end point was relapse-free survival (RFS). Overall survival (OS), toxicity, and quality of life (QOL) were secondary end points. The hypothesis was that UFT was not inferior to CMF in terms of RFS. Results Between October 1996 and April 2001, a total of 733 patients were randomly assigned to receive either treatment. The median follow-up time was 6.2 years. The RFS rates at 5 years were 88.0% in the CMF arm and 87.8% in the UFT arm. OS rates were 96.0% and 96.2%, respectively. The hazard ratios of the UFT arm relative to the CMF arm were 0.98 for RFS (95% CI, 0.66 to 1.45; P = .92) and 0.81 for OS (95% CI, 0.44 to 1.48; P = .49). The toxicity profiles differed between the two groups. The QOL scores were better for patients given UFT than those given CMF. Conclusion RFS and OS with oral UFT were similar to those with classical CMF. Given the higher QOL scores, oral UFT is a promising alternative to CMF for postoperative adjuvant chemotherapy in women with node-negative, high-risk breast cancer.

We report a rare case of a 64-year-old female with metachronous secondary primary left occult breast cancer initially presenting right axillary lymph node metastases. The patient, who had received breast-conserving therapy for left breast cancer at another hospital about 4.5 years ago, came to our hospital complaining of right axillary node swelling. After both breast and systemic examination, she received complete right axillary lymph node dissection. Just after the operation, she was diagnosed with right occult breast cancer by a review of the right axillary lymph nodes and previous left breast cancer. She was followed by radiation and systemic chemoendocrine therapies. One year after axillary lymph node dissection, mammography and ultrasonography showed a new lesion in her left breast. Core needle biopsy revealed similar findings to right axillary lymph node metastasis. After salvage surgery, the diagnosis was revised. We recommend that patients without clinical findings except for axillary lymph node metastasis, especially post-breast-conserving surgery followed by radiation therapy, should be considered not only as having ipsilateral but also contralateral occult breast cancer. If there is no evidence of a primary lesion, axillary lymph node dissection needs to be carried out, and the patient should be offered the choice of radiation therapy or mastectomy followed by proper systemic therapy.

Monoclonal antibodies which are considered to be able to differentiate epithelial and myoepithelial cells in the breast have been developed. Human mammary carcinoma cell line (HBC-4W) was used for immunization. Monoclonal antibodies-B4B2F10 (epi-1), E9E8B7 (myo-l)-with IgM was examined using tissues from diseased breast by avidin-biotin-peroxidase assay. Epi-1 antibody reacted with epithelial cells while myo-1 antibody reacted with myoepithelial cells in the mammary glands, respectively. The reaction was markedly visible, in particular, in fibroadenoma, mastopathy, and papilloma, which showed clear two-cell-type structures. In the infiltrating ductal carcinoma, epi-1 antibody reacted with carcinoma cells, while myo-1 antibody reacted with stromal cells rather than carcinoma cells suggesting that infiltrating ductal carcinoma was mainly of epithelial origin. In the infiltrating lobular carcinoma, however, myo-1 as well as epi-1 antibodies reacted with carcinoma cells. It is suggested that infiltrating lobular carcinoma was of a mixture of epithelial and myoepithelial cell origin. ACTA PATHOL. JPN. 36: 1319–1326, 1986.

We assessed interinstitutional and interobserver consistency of human epidermal growth factor receptor type-2 (HER2) testing using immunohistochemical analysis and fluorescence in situ hybridization (FISH) in a set of 20 breast cancer samples among 10 institutions in Japan and a Herceptin adjuvant study participating laboratory in Germany and identified factors that may lead to discordant results.We found a good agreement in immunohistochemical HER2 scoring between the coordinating institution and 10 participating laboratories (kappa = 0.718) and excellent agreement for FISH (kappa = 0.900). The results of a comparison between 10 Japanese laboratories and the German laboratory was good for immunohistochemical studies (kappa = 0.713) and excellent for FISH (kappa = 0.887). FISH retesting of equivocal samples (2+ immunohistochemically) improved agreement. Discrepancies between results were attributed to the evaluation process in 33.0% of the samples, staining procedures in 25.0%, and a combination of the two in 41.7%. Evaluation of samples according to the American Society of Clinical Oncology/College of American Pathologists guideline increased the number of 2+ immunohistochemical scores. By performing FISH retesting for these samples, consistency among multiple institutions could be archived. The quality of the staining procedures performed and the consistency of evaluations require regular assessment.

Gender identity disorder is defined as persistent feelings of gender discomfort and the inappropriateness of one's anatomical sex. To study the effects of androgens on female breast tissue, we examined mammary glands from female-to-male transsexual (FTMT) women using androgen therapy and from those not using androgen therapy.Female-to-male transsexual breast tissue is a rare specimen in surgical pathology and there are no well-defined guidelines for its examination. We evaluated the clinicopathologic findings of 186 FTMT mammary glands.The patients' ages at presentation ranged from 18 to 49 years (mean 27.4 years). We detected breast carcinoma in only 1 of 130 FTMT women who had not used androgen therapy and in none of 56 FTMT women who had used androgen therapy.We described the histopathological morphology of FTMT breast tissue. The frequency of carcinoma and hyperplasia did not differ significantly between FTMT women who had used androgen therapy and those who had not. These findings suggest that androgen does not alter the risk of carcinoma developing in the mammary glands of FTMT women.

Purpose The clinicopathologic importance of a second estrogen receptor (ER), ER-β, in breast cancers has been intensely studied; however, there is still no real consensus regarding the clinical utility of an ER-β assay, probably because of the lack of standardized methodology, the presence of several ER-β isotypes (ER-β1-5, and so on), and, more importantly, the lack of convincing data on whether the ER-β status provides clinically useful information over what is already provided by the traditional ER-α/progesterone receptor (PR) assay. A large and systematic study is needed to address these important issues. Patients and Methods Archival materials of 442 invasive breast cancers from women treated with adjuvant tamoxifen monotherapy and with a long follow-up period (median, 11.1 years) were subjected to immunohistochemical study using three commercially available anti–ER-β antibodies that detect ER-β1-3 (ER-βN), ER-β1, and ER-βcx (ER-β2). Results Positive staining for ER-βN or ER-β1 was associated with significantly better survival. By contrast, ER-βcx status did not influence survival. In multivariate analysis, ER-β1 status emerged as an independent predictor of recurrence and mortality. ER-β1 status was significantly associated with survival in postmenopausal, but not premenopausal, women. Importantly, ER-β1 positivity was associated with significantly better survival in patients with ER-α–negative/PR-negative or ER-α–negative/PR–negative/human epidermal growth factor receptor 2–negative (triple-negative) tumors, which are widely believed to be hormone unresponsive, have poor prognosis, and require chemotherapy. Conclusion Immunohistochemical examination of ER-β1 in addition to ER-α and PR is clinically important in patients with breast cancer treated with tamoxifen monotherapy. Further studies are needed to confirm our findings.

Primary small-cell neuroendocrine carcinoma of the breast is a rare and aggressive neoplasm without an established treatment protocol because so few cases have been described. We report a case of primary small-cell neuroendocrine carcinoma in a 31-year-old woman. The patient came to our hospital 10 days after consulting another clinic, where a diagnosis of locally advanced breast cancer suitable for neoadjuvant chemotherapy had been made. Core needle biopsy under ultrasonographic guidance revealed invasive carcinoma. The doubling time of the tumor progression was calculated as 12 days based on ultrasonographic measurement. After three cycles of chemotherapeutic regimens consisting of adriamycin plus docetaxel, the disease was judged to be progressive and the patient underwent surgery. Definitive histopathological examination revealed primary small-cell neuroendocrine carcinoma. Local and mediastinal recurrence with multiple liver metastases developed only 5 weeks after surgery. Cisplatin plus irinotecan combination chemotherapy was started; however, the patient died of aggressive recurrent tumor progression 6 months after surgery, in spite of the transient tumor regression achieved by chemotherapy. This case reinforces the importance of an early correct diagnosis and the standardization of a treatment regimen for this very rare tumor.

The PReOperative ‘Arimidex’® Compared with Tamoxifen (PROACT) trial compared neoadjuvant anastrozole and tamoxifen in postmenopausal women with large, operable or potentially operable, locally advanced hormone receptor-positive breast cancer. Here, we compare objective clinical responses with histopathological tumor responses to therapy in a cohort of 97 Japanese patients, in order to investigate the consistency of assessment methods and the change in estrogen-receptor (ER) and progesterone-receptor (PgR) status. Histopathological response and the change in ER and PgR status were assessed by comparing pathological specimens collected at baseline (via needle biopsy) with those collected at 3 months (from excised tumors). The response was evaluated using Pathological Response Criteria for Breast Cancer as defined by the Japanese Breast Cancer Society. The patients were randomized to receive anastrozole (n = 48) or tamoxifen (n = 49). A numerically greater histopathological response rate was observed when neoadjuvant anastrozole compared with neoadjuvant tamoxifen (35.4 and 12.2%, respectively). The histopathological and clinical objective response rates agreed in 63/97 patients. The ER status of 5/40 patients changed from positive at baseline to negative at 3 months in the anastrozole group compared with 20/37 patients in the tamoxifen group. The PgR status of 16/17 patients in the anastrozole group and of 1/11 patients in the tamoxifen group changed from positive to negative. These data support the findings of the main PROACT trial, which confirmed that anastrozole, as compared with tamoxifen, is an effective neoadjuvant endocrine treatment in objective response rates for postmenopausal women with large operable hormone-receptor positive breast cancer. Further follow-up is required to confirm whether histopathological responses to therapy correlate with an overall improvement in survival.

Purpose: To investigate the relationship between the tumor size of breast cancer by palpation and the sensitivity of mammography (MMG) and ultrasonography (US), and which modality can detect nonpalpable breast cancer in women aged 30 to 39 years. Methods: We retrospectively evaluated the tumor size by palpation, breast density, and the sensitivity of MMG and US in 165 patients aged 30 to 39 years. Palpation, US, and MMG were performed with prior knowledge of the results of other modalities. The tumor size on palpation were classified into Tnp; nonpalpable, T1p; 2 cm or less, T2p; more than 2 cm, but not more than 5 cm, and T3p; more than 5 cm. Results: Of 165 patients, 147 patients (89%) showed mammographically dense breasts. Of 165 cancers, 14 (8%) were Tnp, 40 (24%) were T1p, 82 (50%) were T2p, and 29 (18%) were T3p. The sensitivity of MMG was 57% (8 of 14) for Tnp, 78% (31 of 40) for T1p, 90% (74 of 82) for T2p, and 97% (28 of 29) for T3p. The sensitivity of US was 43% (6 of 14) for Tnp and 100% for palpable cancers. Of 14 nonpalpable cancers, 4 (29%), 4 (29%), and 2 (14%) could be detected by only MMG, bloody nipple discharge, and US. Conclusions: The sensitivity of MMG depends on the tumor size on palpation in this age range. MMG fails to detect relatively large palpable cancers. On the other hand, US can detect all palpable cancers. However, the sensitivity of US declines for nonpalpable cancers. For the detection of nonpalpable cancers, MMG, US, and nipple discharge are complementary modalities.

To confirm which modality, ultrasonography (US) or mammography (MMG), is useful to detect breast cancer in women aged 30 to 39 years, and to compare the sensitivity and findings of these two modalities for invasive carcinoma and ductal carcinomain situ (DCIS) in the diagnostic setting. We retrospectively evaluated the sensitivity and findings of these two modalities in 165 patients aged 30 to 39 years, who underwent surgery at the Cancer Institute Hospital between 2001 and 2003. US or MMG were performed after obtaining information on the other modalities previously used and physical examination. The abnormal findings of US were defined as mass lesions and focal hypoechoic areas due to breast cancer. The abnormal findings of MMG were defined as category 3 to 5 (Japanese Mammography Guidelines) masses, calcifications, and other findings due to cancer. Of 165 patients, 147 patients (89%) mammographicaly showed dense breasts. Histologically, 146 (88%) were invasive carcinomas and 19 (12%) were DCIS. In all carcinomas, the sensitivity of US (95%) was higher than that of MMG (85%). The sensitivity of US for invasive carcinoma (99%) was higher than that of MMG (85%). On the other hand, the sensitivity of MMG for DCIS (89%) was much higher than that of US (68%). US is more sensitive to detect breast cancers than MMG in this age range, especially for invasive carcinoma. On the other hand, MMG is useful for detecting DCIS, especially when it manifests with microcalcifications.

In breast cancer, HER-2 overexpression suggests s poor prognosis. Trastuzumab is a humanized monoclonal antibody with specificity to the HER-2 protein. We evaluated the safety and efficacy of combined trastuzumab and paclitaxel therapy in women with metastatic breast cancer.Combination chemotherapy was given to patients with HER-2 overexpressing metastatic breast cancer. All patients had previously received one or more chemotherapy treatments. Patients received a loading trastuzumab dose of 4 mg/kg intravenously (i.v.), followed by 2 mg/kg maintenance dose at weekly intervals. A paclitaxel dose of 80 mg/m(2) was administered on the same day as the trastuzumab infusion.A total of 53 patients were examined. Seventy percent received two or more prior chemotherapy treatments for metastatic breast cancer, and 66.0% of patients had two or more metastatic sites. The overall response rate to our approach was 37.7%. Median time to progression was 12.0 months. Grade 3/4 neutropenia was seen in only 11.3% of patients. Peripheral neuropathy occurred in 65.1% of patients after seven treatments, requiring us to change to biweekly paclitaxel administration in 16 patients. Most of them were able to continue the treatment. Other toxicities were mild and tolerable.Combined trastuzumab and paclitaxel therapy, administered as second-line or later treatment, produced lasting objective responses and was well tolerated by women with HER-2 overexpressing metastatic breast cancer. A major obstacle to continuing treatment was peripheral neuropathy. However, modifying the interval to every 2 weeks enabled us to continue the treatment. This combination chemotherapy was safely performed in our outpatient clinic.

A very rare case of muco-epidermoid carcinoma of the breast is reported. A 54-year-old woman noticed a breast lump and consulted the Cancer Institute Hospital, Tokyo. Physical examination revealed a mass with an unclear margin in the upper outer area of the left breast. Both mammography and ultrasonography showed an irregularly shaped mass, suggesting invasive carcinoma. Aspiration cytology revealed solid clusters of two types of cancer cells: ones with mucus in the cytoplasm, and others without mucus. Cytological features resembled muco-epidermoid carcinoma of the salivary gland but it was not possible to establish a diagnosis of the histological type because muco-epidermoid carcinoma of the breast had not previously been encountered by the authors. After incisional biopsy, left mastectomy with axillary lymph node dissection was performed. Histologically the tumor was surrounded by a fibrous pseudocapsule and was composed of intraductal carcinoma foci and invasive cancer nests. Intraductal carcinoma foci were the low papillary type. Stromal invasion showed many solid nests composed of mucus-containing and squamoid cancer cells. There was no common invasive ductal carcinoma component in this tumor. These histological features confirmed the diagnosis as muco-epidermoid carcinoma of the breast. This is the first report of muco-epidermoid carcinoma of the breast in Japan.

Background & Aims: The purpose of this study was to investigate the influence of pregnancy on breast\ncancer prognosis by analyzing clinical and pathological features of young patients with breast cancer in\nrelation to last birth. Method: A total of 622 young breast cancer patients under 35 years of age\nundergoing surgical treatment between 1960 and 1990 at Cancer Institute Hospital were included in this\nstudy. The patients were classified into four groups; group A patients who were diagnosed during\npregnancy or within one year after delivery, group B patients who were diagnosed from one to three years\nafter delivery, group C patients who were diagnosed three years or more after delivery, and group D\npatients who were nulliparous. All four groups were examined from the viewpoint of clinical and\npathological findings with regard to age, disease duration, first childbirth, clinical stage, histopathological\ntype, lymph node metastasis, and survival. Furthermore, nuclear grade and immunohistochemical\nstaining of both estrogen receptor (ER) and factor-VIII were examined in early-stage breast\ncancer patients. Result: The incidence of early-stage(0, I and II) breast cancer was significantly(p＜\n0.05) lower in group A (69％) than in groups C (88％) and D (85％). The incidence of nodal involvement\ndecreased from group A (61％), B (59％), C (51％) to D (43％) in that order. The incidence of\nnodal involvement in group D was significantly (p＜0.05) lower than that in groups A and B. The\npositive rate of estrogen receptor increased from group A (50％), B (56％) to C (72％) in that order. \nDisease-free survival was significantly (p＜0.05) more favorable in group D than in groups A and C. \nThe similar result was obtained in patients with clinically early-stage breast cancer. Conclusion:\nPatients who developed breast cancer during pregnancy or within less than one year postpartum have a\npoor prognosis among patients under 35 years old. Patients having no childbirth history generally have\na high risk factor of developing breast cancer, however, breast cancer patients without childbirth history\nunder 35 years old result in a favourable prognosis.

Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. Although the survival of patients with IBC has been greatly improved by the use of combined treatment modalities, women with IBC still have lower survival rates. We have summarized a single-center experience involving IBC patients. Our objectives are to clarify molecular alterations of HER- 2/neu and p53 in IBC and to investigate the prognostic factors. Between January 1990 and December 2000, 57 patients with IBC were referred to the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The incidence of IBC among primary breast cancers was 1.0% (57/5,757) in our hospital. Forty-six patients meeting Haagensen's criteria for inflammatory breast carcinoma were evaluated. All patients had biopsy-proven carcinomas but no distant metastases at referral. The median age at diagnosis for IBC was 51.8 (range, 28 to 70). All patients underwent a mastectomy. Chemotherapy was performed pre-or postoperatively. Three-year and 5-year survival rates were 56.5%, and 40.7%, respectively. Expressions of HER- 2/neu and the p53 protein were determined retrospectively by immunohistochemical (IHC) staining of thin paraffin-embedded sections of primary tumors. Of 46 patients, 23 (50.0%) with tumors testing positive for HER-2/neu fared somewhat worse than those with negative tumors, but the differences were not significant for either overall survival (OS) or disease-free survival (DFS). Of 46 patients, 19 (41.3%) whose tumors were positive for p53 fared somewhat better than patients with negative tumors, with no significant differences in either OS or DFS. Patients presenting with less than ten pathologically involved axillary lymph nodes showed significantly better OS and DFS. Overexpression of HER-2/neu and the p53 protein were not significant prognostic factors in inflammatory breast cancer. However, the increased incidence of HER-2/neu and the poor outcome of IBC may be of clinical interest, suggesting the need for clinical trials of antibody therapy targeted to HER- 2/neu. Moreover, a high prevalence of p53 may be useful in determining the specific use of chemotherapy.

Context: Aromatase, steroid sulfatase, and 17β-hydroxysteroid dehydrogenase type 1 (HSD-1) peripherally up-regulate, whereas estrogen sulfotransferase (EST) and HSD-2 down-regulate, the synthesis of active and more potent estrogens. These estrogen-metabolizing enzymes (EMEs) are important in postmenopausal breast cancers, but have never been systematically examined in breast cancers of the elderly. Objective and Design: mRNA levels of EMEs in cancerous and normal breast tissues from 39 elderly patients (age, 80–99 yr) were compared with those from 39 controls (age, 37–70 yr) or compared according to estrogen (ER)/progesterone (PR) receptor status. Results: Aromatase levels were higher in cancers of the elderly (EldCa) than in normal tissue of the elderly (P = 0.0008) or cancers of controls (P = 0.0033). In contrast, levels of steroid sulfatase and EST were higher in cancers of controls than normal tissue of controls (P = 0.0046 and P < 0.0001, respectively) or EldCa (P = 0.0001 and P < 0.0001, respectively). Levels of HSD-1 and HSD-2 did not differ significantly between any two of the categories. Among EldCa, HSD-1 levels were higher in ER/PR-positive than in ER/PR-negative carcinomas, whereas EST and HSD-2 exhibited opposite results. Conclusions: The importance of aromatase is relatively increased in EldCa. ER/PR-positive EldCa exhibited a pattern of EMEs more beneficial to the production of estrogen than did ER/PR-negative EldCa. The specific pattern exhibited in EldCa may elucidate the role of EMEs in the absence of ovarian estrogens in the pathogenesis of breast cancer.

Aims : Apocrine carcinoma of the breast is typically, though not always, positive for gross cystic disease fluid protein-15 (GCDFP-15). In order to clarify the clinical significance of GCDFP-15 in apocrine carcinomas, GCDFP-15 expression was examined in apocrine carcinomas of different stages and compared with clinicopathological factors. Apocrine lesions reportedly exhibit an unusual immunohistochemical status, expressing androgen receptors (AR) instead of oestrogen receptors (ER), progesterone receptors (PR), or bcl-2. Their expression was also examined. Methods and results : Fifty-two apocrine carcinomas were examined immunohistochemically. Thirty-nine (75%) and 29 (56%) were positive for GCDFP-15 and AR, respectively. GCDFP-15 positivity was significantly lower in infiltrating carcinomas than intraductal carcinomas (P = 0.0111). In infiltrating carcinomas, GCDFP-15 positivity was significantly low in tumours ≥ 15 mm (P = 0.0005) and node-positive tumours (P = 0.0004). Similar phenomena were observed for AR. Rare cases were positive for ER (3.8%), PR (5.8%), and bcl-2 (1.9%). Conclusions : GCDFP-15 positivity is transient and should not be considered a definitive marker of apocrine carcinomas. Cases which have apocrine features but lack GCDFP-15 expression should rather be considered as advanced apocrine carcinomas. ER/PR/bcl-2 negativity will sometimes be helpful to confirm the diagnosis of apocrine carcinoma, because it is more consistent than GCDFP-15/AR positivity.

In Japan, postoperative relapse occurs within five years in 9.2 to 16% of patients whose breast cancers have not metastasized to lymph nodes at the time of initial surgery(node-negative, n0). Attempts to find molecular markers able to classify n0 breast cancers in terms of postoperative prognosis have not been successful.To identify molecular indicators of prognosis for this type of cancer, we used a cDNA microarray consisting of 25,344 human genes to investigate expression profiles of 12 primary breast cancers from patients whose tumors recurred within five years after surgery(5Y-R) and 12 from patients who survived disease-free for more than five years (5Y-F).Sets of genes characterizing each group in terms of expression patterns in the tumors were selected by Mann-Whitney and random-permutation tests: these panels included 21 genes expressed highly in 5Y-R tumors than in 5Y-F tumors, and 37 with higher expression in the 5Y-F group than in the 5Y-R group.We established a scoring system to prediction of postoperative prognosis which was 100% accurate as to the actual clinical outcomes of the 24 cases and therefore might be useful for predicting prognosis of n0 breast cancers in a clinical setting. The prognostic score system clearly separated the two groups without any overlap, and accurately predicted prognosis in 6 additional cases. Moreover, the extensive list of tumor-related genes identified in these experiments provides valuable information about progression of breast cancer and suggests potential target molecules for therapy of n0 breast cancers.

Healing is a phenomenon by which the intraductal component of breast cancer disappears and is replaced by fibrous tissue. Focally localized healing often prevents confirmation of the continuity of intraductal carcinoma. To clarify the clinicopathological characteristics of breast cancer with healing. At our hospital, 308 patients (311 breasts) underwent breast conservation therapy without neoadjuvant chemotherapy for breast cancer in 2000. These surgical specimens were histopathologically investigated with 5 mm serial sections. We assessed the proportion and the characteristics of breast cancer with healing. (1) The proportion of breast cancer with healing was 7% (21/311). (2) In the 21 patients, the mean age was 59.2 years, and the mean diameter was 2.8 cm. (3) The histological type of the breast cancer varied: noninvasive ductal carcinoma in 2 cases, papillotubular carcinoma in 5, solid-tubular carcinoma in 8, scirrhous carcinoma in 5, invasive lobular carcinoma in 1, and Paget’s disease in 1. However in all cases, the histologic type of the intraductal carcinoma foci was the comedo/solid type and the nuclear grade of cancer cells was high. (4) In cases with healing, areas of healing were seen in an average of 5 (1-26) blocks, compared with intraductal carcinoma foci in 13 blocks (2-40). Healing was located on the nipple side of the main lesion in 8 cases, the peripheral side in 9, and both sides in 4. In 3 cases, healing was seen at the surgical margin of the partial mastectomy specimen. The proportion of breast cancer cases with healing was 7% and these cases were intraductal carcinoma of the comedo/solid type, consisting of highly malignant cancer cells.

Medullary carcinoma (MC) of the breast is characterized by large anaplastic cells and infiltration by benign lymphocytes. Patients with this pattern of breast carcinoma are considered to have a better prognosis than those with other histological subtypes. We reviewed cases of primary breast carcinoma that were surgically resected between 1990 and 2004. Of these, 13 cases of medullary carcinoma of the breast with lymphocyte infiltration were reported. Tests for CD3, CD4, CD8, CD20, CD56, TIA-1, and granzyme B were performed on paraffin sections. We found that the MC contained very few NK cells, as assessed by their reactivity with the CD56 antibodies. However, MC had a significantly greater percentage of CD3, CD8, TIA-1, and granzyme B lymphocytes infiltrating the stroma of the tumor. Furthermore, more CD8-positive than CD4-positive T-cell lymphocytes were present within the tumor cell nests in MC, as opposed to the proportion in usual ductal carcinoma. The infiltrating cytotoxic/suppressor T cells in MC represent host resistance against cancer, and the high grading of the T-cell infiltration could explain, in part, a key mechanism controlling the good prognosis for this type of tumor and solve the pathological paradox of MC.

In order to accurately determine the expression of thymidine phosphorylase (TP) in breast cancer, it is important to develop an appropriate system for immunohistochemical staining evaluation. Three raters, pathologists A-C, independently judged the status of TP in both cancer cells and cancer stromal tissue in 586 breast cancers immunohistochemically. TP expression levels were categorized into four groups (scores 0-3), and scores of 2 and 3 were considered as positive. Interrater and intrarater agreement levels in the judgment of TP expression were analyzed by the kappa statistics. By combining three raters' judgments, we sought for the optimal evaluation system that generates the best concordance among all judgments. The numbers of TP-positive cases were 294 (50.2%), 309 (52.1%) and 344 (58.7%) for cancer cells and were 315 (53.8%), 383 (65.4%) and 397 (67.7%) for cancer stromal tissue in the judgments by pathologists A, B, and C, respectively. There was no correlation of TP immunostaining between cancer cells and cancer stroma tissue. Interrater agreement levels were substantial for cancer cells (kappa = 0.652) and moderate for cancer stroma tissue (kappa = 0.438). Intrarater agreement level for TP judgment by pathologists A, B, or C was substantial to almost perfect for cancer cells (kappa = 0.755-0.880), and for cancer stromal tissue (kappa = 0.620-0.752). The level of TP expression estimated under the majority system and the total scoring system setting a cut-off score between 4 and 5 revealed the highest concordance with the three raters' judgments. To accurately evaluate the TP status in breast cancer tissue, three or more raters are needed and the majority system and total scoring system appear appropriate.

Adenoid cystic carcinoma (ACC) is rare in breast carcinomas and has a relatively better prognosis than other histological types. Although the tumor shows various growth patterns, such as those of salivary glands or other organs, the papillary growth pattern is uncommon. Collagenous spherulosis (CS), consisting of intraluminal clusters of eosinophilic spherules situated adjacent to, or encompassed by, usually benign proliferative epithelium, is also a rare incidental microscopic finding that ACC must be distinguished from, and it has never been reported in association with ACC. We present a case of ACC arising in mammary ducts with the papillary growth pattern and CS-like structures that should not be mistaken for benign proliferative lesions, especially in the core needle-biopsy specimen, because the adenoid cystic pattern might not always be contained in the specimen. Morphologically and histochemically, the results suggest that the CS-like structures in the present case undergo a similar process to the originally described CS, which the myoepithelium is thought to be associated with. Examination of more cases are necessary to clarify the process of CS and its relationship to mammary proliferative lesions.

Invasive micropapillary carcinoma(IMC)of the breast is a rare subtype of breast carcinoma that has an extremely high incidence of lymph node metastases and poor clinical outcome. This histological subtype of breast carcinoma has remained unclear due to the rarity of cases. Many questions exist on the clinicopathological significance of this subtype, especially regarding prognosis.We reviewed all 671 cases of primary breast carcinoma that were surgically resected at our institute between 1990 and 2004. Of these, 27 cases of invasive ductal carcinoma of the breast with a pure or partial micropapillary component were reported. The cases were analyzed using various parameters, including age at presentation, tumor size, tumor grade, presence of lymphatic invasion, and axially lymph node status.The patients' age at presentation ranged from 31 to 74 years (mean 52.4 years). Tumor size ranged from 0.7 to 10 cm (mean 4 cm). 88.9% (24 of 27) of the cases had lymphatic invasion. Of cases who underwent with axillary dissection, 66.6% (18 of 27) had positive lymph nodes. Clinical follow up data were available for 17 cases with IMC for 1 to 72 months. Among these, 10 patients died from breast carcinoma within 5 years.While our series is too small to make conclusions about the behavior of IMC, the difference in 6-year survival rate between the patients with IMC and those with breast carcinoma in general was statistically significant. Recognition of this distinctive and aggressive variant of infiltrating carcinoma is important because of its poor prognosis and high incidence of lymph node metastases.

Estrogen receptor (ER) status is an essential determinant of clinical and biological behavior of human breast cancers. While ER-positive breast cancers respond well to adjuvant hormone therapy, ER-negative tumors are generally resistant. To date, no attempts have succeeded in finding molecular markers for classifying ER-negative breast cancers with respect to postoperative prognosis. To identify a set of prognostic markers for this type of cancer, we used a cDNA microarray consisting of 25,344 human genes to investigate expression profiles of ten primary breast cancers from patients who had died of breast cancer within 5 years after surgery (5y-D) and 10 from patients who had survived disease-free for more than 5 years (5y-S). Sets of genes characterizing each group were identified by Mann-Whitney and random-permutation tests. We documented 71 genes with higher expression in the 5y-D group than in the 5y-S group, and 15 with higher expression in the 5y-S group than in the 5y-D group. Semi-quantitative RT-PCR experiments were carried out to confirm the results of the microarray analysis. We established a scoring system for predicting postoperative prognosis of ER-negative breast cancers on the basis of aberrant gene expression. The list of genes reported here provides valuable information with regard to progression of breast cancer and is a source of possible target molecules for development of novel drugs to treat patients with ER-negative breast cancers.

Aims and background We evaluated retrospectively the efficacy and toxicity of paclitaxel in patients with docetaxel-resistant metastatic breast cancer. Study design Paclitaxel (80 mg/m2) was administered weekly to 44 patients who had previously received chemotherapy regimens for metastatic breast cancer. All patients had progressive disease in spite of having received docetaxel therapy. Results Treatment was repeated until there was evidence of disease progression. Objective responses were obtained in 14 of 44 assessable patients (31.8%; 95% confidence interval, 17.5–46.1). Fourteen patients had partial responses; none responded completely. Seven of 14 responders had primary resistance to docetaxel therapy. The median duration of response was 6.1 months (range, 2.1–12.7). The median time to progression was 5.0 months. Clinically severe adverse events (grade 3 or 4) included neutropenia (27.2%), leukopenia (25.0%), neuropathy-sensory (13.6%), febrile neutropenia (6.8%), anemia (2.2%), constipation (2.2%), and edema (2.2%). Treatment was generally well tolerated and could be continued on an out-patient basis. Conclusions Weekly paclitaxel is effective in patients with docetaxel-resistant metastatic breast cancer. This observation suggests partial cross-resistance between paclitaxel and docetaxel. There was no evidence for additive cumulative toxic effects of the two taxanes.

To assess the presence of invasion in non-palpable breast cancer with microcarcifications. We investigated 157 patients with non-palpable breast cancer with microcalcifications, who had undergone stereotactic core biopsy or vacuum-assisted breast biopsy and operation at the Cancer Institute Hospital between 1995 and 2001. We investigated the correlation between the area of calcification (maximum range of microcalcifications measured in mm by direct mammograhy), morphology of calcification on mammography, histological subtype of intraductal carcinoma (comedo or non-comedo) and frequency of invasion, and lymph node metastasis. The chi-square test was used in the statistical analysis andp values less than 0.05 were considered statistically significant. Invasion was observed in 33 of 157 pts (21%), of whom 23 showed minimal invasion, which is less than 0.5 cm in greatest diameter. The risk of invasion was 13% within 10 mm of the microcalcifications (n = 70), 25% from 11 to 30 mm (n = 59), and 32% more than 31 mm from the microcalcifications (n = 28). The risk of invasion was 16% for punctate-round and amorphous type (n = 87) microcalcifications, and 27% for pleomorphic and linear-branching types (n = 70) (p = 0.092). In addition, invasion was found 10% of the time within 10 mm of punctate-round and amorphous type microcalcifications, and 20% of the time at 11 mm or more. On the other hand, invasion was found 15% of the time within 10 mm of pleomorphic and linear-branching type microcalcifications, and 37% of the time at 11 mm or more. In 72 cases of intraductal carcinoma diagnosed by pathological examination, invasion was found in 10 of 31 (32%) comedo type intraductal carcinomas and in 5 of 41 (12%) non-comedo types(p = 0.0379). There were 5 cases (3.2%) with axillary lymph node metastasis, all of which widely extended more than 21 mm from the microcalcifications. The risk of invasion was 10% within 10 mm of punctate-round and amorphous type microcalcifications, and 37% at more than 11 mm of pleomorphic, linear-branching microcalcifications.

乳癌の内分泌療法における効果予測因子は癌細胞のホルモンレセプターの有無であり,真のレセプター状況を把握し,治療の選択を決定することが必要である.今回,乳癌手術症例で生化学的方法(EIA法)および免疫組織化学染色法(IHC法)でエストロゲンレセプター(ER)状況を判定した316例を対象に, EIA法とIHC法でのER陽性率と一致率を調べ,問題点を検討した. EIA法でのER陽性率は43%, IHC法では66%で,一致率は75%であった.硬癌,粘液癌などの細胞密度の低い組織型ではEIA法では偽陰性となる可能性が示された.また, ER陽性の正常乳管上皮の影響も考えられ,顕微鏡で直接癌細胞を確認できるIHC法はEIA法よりも有用であった.今後, IHC法の判定基準の統一が必要であるが,過去にEIA法で陰性であった症例も,転移再発時には以前の手術時のパラフィン切片を用いてIHC法で再検査することによって,治療の選択肢が広がる可能性が示唆された.

Aims and background The human epidermal growth factor receptor 2 (HER2) protein is a unique and useful target for antibody therapy against breast cancers that overexpress the HER-2/neu gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab, was approved for clinical use in the United States in 1998. It became available in Japan in June 2001. This study focuses on the efficacy and safety of trastuzumab as a single agent in second-third line treatment of HER2/neu-overexpressing metastatic breast cancer. Study design Between June 2001 and May 2002, we treated 62 patients with trastuzumab, as a single agent or in combination chemotherapy, for second-third line treatment of HER2-overexpressing metastatic breast cancer. Twenty-seven of 62 patients were treated with trastuzumab as a single agent. We reviewed retrospectively the efficacy and safety of the drug given as a single agent. The expression of HER2 was determined by immunohistochemical staining. All patients received a standard loading dose of 4 mg/kg followed by 2 mg/kg weekly. Results Patients received a median of 16.7 weekly infusions (range, 1–66 infusions). Trastuzumab therapy was generally well tolerated. Clinically severe adverse events (grade 3 or 4) included hypotension (7.4%), and hypoxia (3.7%). Grade 1 to 2 toxicity included fever (11.1%) and diarrhea (3.7%). Infusion-related reactions were infrequent, as were serious hematologic complications. Cardiotoxicity did not occur in the study. Three patients had a complete and 3 a partial response, 3 had no change, 17 had progressive disease, and one was not evaluated. The overall response rate in the 26 patients with available data was 23.1% (95% confidence interval, 5.7–40.4). The median duration of response was 6.4 months (range, 2.5–14.0). The median time to progression was 3.1 months (range, 0.2–16.7). Response rates differed by metastatic site as follows: lung 0% (0/12), bone 10.0% (1/10), liver 0% (0/8), skin 50.0% (4/8), lymph nodes 42.9% (3/7), brain 0% (0/2). Conclusions Molecular target therapy with trastuzumab appears safe and is generally well tolerated. For treatment of metastatic breast cancer, single agent therapy produces a durable response in some patients but lacks sufficient efficacy. Single agent use of trastuzumab is a viable option for treatment in cases with non-life-threatening disease without visceral metastasis.

Sentinel node (SN) biopsy is a promising replacement for standard axillary lymph node dissection for the staging of early breast cancer, and various techniques have been studied to identify SNs with dye or radioactive colloid. This study assesses the effect of the dose of radioactivity and the time before biopsy in order to set standards for the use of 99mTc-rhenium sulphide for the detection of SNs in breast cancer patients. Sixty patients with stage T1-2 N0 M0 breast cancer underwent SN biopsy, which was immediately followed by standard axillary dissection to confirm the SN results. For SN biopsy, 99mTc-rhenium colloid was injected peritumorally. A 1 day (morning injection and afternoon surgery) or 2 day (day before afternoon injection and morning surgery) protocol was applied. A dose-finding study was performed simultaneously using 7.4-37 MBq for the 1 day protocol and 37-74 MBq for the 2 day protocol. A scintigram was taken at 2 h for the 1 day protocol and 16 h for the 2 day protocol. After the injection of blue dye, SN biopsy was performed with a gamma probe, followed by standard axillary node dissection. The radiation exposure received by the surgical team during the operation was monitored. Histopathological comparison between SNs and axillary nodes was performed. Patient characteristics that might affect the radiocolloid uptake by SNs were assessed. SNs were identified in all patients regardless of the dose or administration protocol used. Two patients showed false negative pathological SN results, and the negative predictive value was 96% and the positive predictive value was 100%. In addition, radiation exposure to the surgical team and the amount of radioactive surgical waste were low, especially at lower doses. Two groups of patient characteristics were related to SN uptake. One was the body mass index (BMI) and the other was the age or menopausal status. Patients with a larger BMI tended to take up a smaller amount of 99mTc colloid. Older or post-menopausal patients showed lower SN uptake. 99mTc-rhenium sulphide colloid is an efficient radiopharmaceutical for SN detection. Both 1 day and 2 day protocols have equally good efficacy, and the recommended dose is 7.4 MBq for the 1 day protocol and 37 MBq for the 2 day protocol. Patients with larger BMI and older or post-menopausal patients tend to take up less 99mTc colloid.

A 45-year-old man developed a bloody discharge from his right nipple. Physical examination revealed bloody discharge from his left nipple also but no swelling, breast mass, or axillary lymph nodes. He then underwent bilateral total glandectomy without axillary dissection. Histological examination revealed low-grade ductal carcinoma in situ (DCIS) with a low-papillary and cribriform pattern measuring about 4 mm in diameter in the breast bilaterally. To our knowledge, this is the first report of synchronous bilateral DCIS in a male. Since this patient's hormonal profile showed a relatively high blood level of prolactin, the causative relationship between hyperprolactinemia and male breast cancer is discussed. Including our case, 5 of 6 cases reported thus far have been bilateral, and 4 of the 6 cases have been synchronous. We emphasize that the contralateral breast should also be tested or followed in male breast cancer patients with hyperprolactinemia.

Aims: The pathogenesis of breast carcinoma in very elderly women is of interest, because oestrogen levels are likely to be extremely low during the development of the disease. In an effort to understand the pathogenesis of breast carcinoma in these women, this study was undertaken to compare the histological patterns and hormone receptor status of breast carcinomas arising in very elderly and younger women. Methods and results: Thirty-seven breast carcinomas from women over the age of 85 years at the time of their operation were examined histologically and compared with those from a large group of premenopausal women. The proportions of mucinous carcinoma and apocrine carcinoma were significantly greater in older women. The expression of steroid hormone receptors was studied immunohistochemically. Androgen receptor-positive carcinomas were significantly more frequent among older women, whereas progesterone receptor-positive carcinomas were significantly less frequent. There was no statistically significant difference in oestrogen receptor-α or -β expression between the tumours from both groups. Conclusion: Breast carcinomas in women over the age of 85 years have a different morphological spectrum from carcinomas in younger age groups and may have different pathogenesis mechanisms that may be more dependent on androgen and androgen receptor interaction. Differences from the results of the other studies are discussed.

Background: Although many clinical data regarding breast-conserving treatment have already been reported from European and North American countries, few clinical data with long-term follow-up have been reported from Japan. Method: We collected information on therapeutic and possible or developed prognostic factors and follow-up data for Japanese women who had received breast-conserving treatment consisting of wide excision of the primary tumor, axillary dissection and radiotherapy for unilateral breast cancer considered suitable for breast-conserving treatment from 18 Japanese major breast cancer treating hospitals; 1561 patients were registered. Results: The median follow-up period was 77 months. Five-year disease-free and overall survival rates were 89.4 and 95.9%, respectively. The 5-year local recurrence-free rate was 96.3%. The patients with histologically positive margins (P < 0.0001) or estrogen receptor negative tumor (P = 0.0340) or younger than 40 years old (P < 0.0001) developed statistically significantly more local recurrences. Adjuvant endocrine therapy was essential for the estrogen receptor positive patients to have a lower local recurrence rate. Endocrine therapy did not change the local recurrence rate among estrogen receptor negative patients at all. Multivariate analysis showed histological margin status and the combination of estrogen receptor status and endocrine therapy were independent prognostic factors for local recurrence. Conclusion: The 5-year local recurrence rate of Japanese breast cancer patients who were treated with breast-conserving treatment using radiotherapy was 3.7%. Independent prognostic factors for local recurrence were histological margin status and the combination of estrogen receptor status and adjuvant endocrine therapy.

To diagnose intraductal lesions endoscopically the Japanese Association of Mammary Ductoscopy classified the endoscopical appearance of lesions into three types. We investigated the correlation between endoscopic classification and histological diagnosis.From April 1998 to February 2001, we enrolled 129 female patients who were diagnosed histologically and whose intraductal lesions were detected by mammary ductoscopy. The endoscopic classification consists of three types. The polypoid type is a localized expansive lesion. This type is divided into two subtypes, the solitary subtype (solitary polypoid lesion) and the multiple subtype (multiple polypoid lesions). The combined type is polypoid lesion(s)coexisting with a superficial type. The superficial type is a superficial spreading lesion such as a continuous luminal irregularity accompanied by no obvious elevations.There were 65 cases of breast cancer and 64 cases of benign papillary lesions. Fifty-four cases of benign papillary lesions and 7 cases of breast cancer were classified as the polypoid-solitary type. Seven benign cases and 13 cases of cancer were classified as the polypoid-multiple type. Two benign cases and 16 cases of cancer were classified as the combined type. Only one benign case and 29 cases of cancer were classified as the superficial type. There is significant correlation between endoscopical types and the histological diagnosis (p0.0001).Endoscopic classification is useful to diagnose intraductal lesions.

To identify specific allelic losses that might correlate with postoperative mortality of breast cancer patients treated with high-dose adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil, we examined tumors from a cohort of 150 such patients, who were followed clinically for 5 years postoperatively, for allelic losses (loss of heterozygosity, LOH) among 18 microsatellite markers throughout the genome. Patients whose tumors had lost an allele at 8p22 had significantly higher risks of mortality than those whose tumors retained both alleles at those loci. At 8p22, the 5-year mortality rate was 31% among patients with losses vs. 8% with retention (P=0.0354). No other region showed correlation between LOH and prognosis. The data indicate that LOH at 8p22 is a significant predictor of postoperative mortality for breast cancer patients who received high-dose postoperative adjuvant chemotherapy. Thus, LOH at 8p22 can serve as a negative prognostic indicator to guide postoperative management of patients.

To examine interobserver reproducibility in the judgments of HER-2/neu (c-erbB-2) oncoprotein expression, HER-2/neu expression was scored immunohistochemically. A total of 106 breast carcinomas were independently scored by five or six pathologists, using four commercially available anti-bodies (HercepTest, Nichirei polyclonal antibody, CB11 and TAB250). Two systems were used for the evaluation. In the Dako system, the intensity of membrane staining was primarily evaluated whereas in the Tohoku system, the area of the membrane-staining-positive cells was primarily evaluated. All four antibodies gave excellent concordance rates among the pathologists' judgments of the scores. Using the HercepTest and Nichirei polyclonal antibody, dividing the cases into two groups designated score 3+ and score 0/1+/2+ achieved a higher percentage of concordant cases than division into groups designated score 2+/3+ and score 0/1+. Using the HercepTest, the Dako system tended to achieve higher concordance than the Tohoku system. Conversely, CB11 and TAB250 showed similar concordance rates under both the Dako and the Tohoku systems, regardless of how the cases were divided. High interobserver agreement levels were achieved only when HER-2/neu overexpression was defined as a score of 3+, using any of the antibodies; these were similar between the Dako system and the Tohoku system. Positivity by TAB250 was lower than that by CB11. Using the HercepTest and Nichirei polyclonal antibody, cases with a score of 3+ almost always achieved complete interobserver agreement and showed HER-2/neu gene amplification. Conversely, cases with a score of 2+ achieved a low percentage of interobserver agreement and showed no gene amplification. Because judgment of a case as score 2+ was not very reproducible, and a score of 3+ was of biological significance and had high interobserver reproducibility, we suggest that only a score of 3+ be considered as overexpression. When cases of score 2+ are entered into a protocol, evaluation should be given by multiple observers and/or by using other tests such as fluorescence in situ hybridization.

To identify specific allelic losses that might correlate with postoperative mortality of patients with node-positive breast carcinomas, we examined tumors from a cohort of 263 such patients, who were followed clinically for 5 years postoperatively, for allelic losses among 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 13q12, or 17p13.3 had significantly higher risks of mortality than those whose tumors retained both alleles at those loci. At 3p25.1, the 5-year mortality rate was 33.8% among patients with losses vs. 16.8% with retention (P = 0.0154); at 13q12, 30.3% vs. 13.0% (P = 0.0241); and at 17p13.3, 30.4% vs. 16.2% (P = 0.0243). Combined losses at 3p25.1 and 17p13.3 increased the predicted postoperative mortality risk by a factor of 4.9 (5-year mortality rate of 38.2% vs. 8.0%, P = 0.0006), and combined losses at 3p25.1 and 13q12 raised the predicted postoperative mortality risks by a factor of 2.9 (34.7% vs. 12.7%, P = 0.0441). These data indicate that loss of heterozygosity (LOH) at any one or a pair of loci at 3p25.1, 13q12, or 17p13.3 is a significant predictor of postoperative mortality for breast-cancer patients.

Leiomyomas are common in the genitourinary and gastrointestinal tracts and less frequent in skin and soft tissue. It is quite uncommon for them to develop in the breast, especially in the breast parenchyma. Only 12 cases of leiomyoma in the breast parenchyma proper apart from the areola have been reported. We present a thirteenth case, the first to be reported in Japan. Its clinical features, mammographic and ultrasonographic findings, histological and immunohistochemical characteristics are quite consistent with previous reports.

BACKGROUND Fluorescent in situ hybridization (FISH) has been shown to be one of the most reliable methods with which to estimate the status of the HER-2/neu (or c-erb B-2) oncogene at the DNA level. METHODS To study interobserver reproducibility and to determine more clinically correlated criteria for HER-2/neu alterations, two observers independently estimated HER-2/neu DNA status. The correlation between the consensus HER-2/neu DNA status by FISH and HER-2/neu protein status detected by immunohistochemistry (IHC) using a polyclonal antibody was studied in 216 surgically resected breast carcinomas and 34 noncancerous tissues. RESULTS According to the HER-2/CEP17 ratio and mean HER-2 copies per nucleus, agreement level of HER-2/neu amplification was shown to be nearly perfect between two observers (kappa statistic (κ) = 0.94 and κ = 0.84). Finally, 40 tumors (19%) were judged to have HER-2/neu DNA amplification, with 6 having low-level amplification (≥ 2 but < 3 folds) and 34 having high-level amplification (≥ 3 folds). One hundred seventy-six other tumors, including 3 tumors that only 1 of the observers determined to be low-level amplifiers, and 34 noncancerous tissues had no detected amplification. The DNA amplification status was concordant between invasive and intraductal components in 14 carcinomas. HER-2/neu protein overexpression of moderate (2+) or high (3+) intensity based on IHC was detected in 51 carcinomas (24%), and was 2+ in 20 carcinomas and 3+ in 31 carcinomas. The HER-2/CEP17 ratio of ≥ 2 was concordant with IHC findings of 2+/3+ in 91% of carcinomas (195 of 215 carcinomas), with a sensitivity of 70% (35 of 50 carcinomas) and a specificity of 97% (160 of 165 carcinomas). High-level amplification was detected in 29 of 31 IHC 3+ cases (94%), but in only 5 of 20 IHC 2+ cases (25%) and 0 in 165 IHC 0/1+ cases. All 34 cases with high-level amplification showed an IHC score of 3+ (29 cases) or an IHC score of 2+ (5 cases), but only 1 case was found to have an IHC score of 3+ and the remainder were IHC 0/1+ in 6 low-amplification cases. The concordance rate of the high-level amplification with an IHC score of 3+ was 97% (208 of 215 cases), with a sensitivity of 94% (29 of 31 cases) and a specificity of 97% (179 of 184 cases). CONCLUSIONS The results of the current study indicated that high-level HER-2/neu amplification and an IHC score of 3+ nearly optimally identified breast carcinomas with clinically and biologically significant HER-2/neu activation. Conversely, it was confirmed that careful interpretation of test results is required in the case of low-level amplification and/or an IHC score of 2+. Cancer 2001;92:2965–74. © 2001 American Cancer Society.

がん検診の施行主体が自治体に委ねられた現在, 検診の精度管理がいかに行われるかは課題である。特に乳癌検診へのマンモグラフィ導入にあたっては, 撮影・読影などについての精度管理が必要であり, この精度管理システムの確立なくしてマンモグラフィ検診は成り立たない。日本乳癌検診学会を中心に関連学会の協力のもと, マンモグラフィ検診精度管理中央委員会を設置し, 本委員会には教育・研修委員会と施設・画像評価委員会の小委員会を設置した。本委員会は他臓器がん検診にはみられない, 本邦では初めてのシステムである。教育・研修委員会はすでに活動を開始し, 医師・技師に対して診断精度を一定に保つために読影, 撮影などの教育研修を実施している。さらに施設・画像評価委員会も検診実施機関に対して診断機器や画質などの評価を行う予定である。今回の厚生省から出された「がん予防重点健康教育及びがん検診実施のための指針」および「がん検診実施上の留意事項」の中に精中委の位置付けが示され, 本精中委が他臓器がん検診には見られないシステムとして行政に認知された。今後, この精度管理中央委員会への社会的認知と各地域の「精度管理委員会」との連携が重要なポイントといえる。

Background and Objectives The UICC and the Japanese Breast Cancer Society have different TNM classifications. There is a large discrepancy between the pathological node status in the UICC (UICC-NS) and JBCS (JBCS-NS) systems. We compared the UICC-NS with the JBCS-NS. Methods Reviewed were data on 1,684 invasive ductal carcinomas at the Cancer Institute Hospital from 1981 to 1986. Each case was categorized according to the UICC-NS and JBCS-NS, respectively. Overall survival 10 years after surgery (OS) by UICC-NS and JBCS-NS was calculated by the Kaplan–Meier method. Results OS with UICC-NS and number of case were, respectively, 87.8% and 968 for pN0, 83.9% and 93 for pN1a, 71.6% and 190 for pN1bi, 60.0% and 25 for pN2, 58.8% and 51 for pN1bii, 55.7% and 238 for pN1biii, 54.2% and 24 for pN1biv, 44.8% and 58 for pN3, and 20.6% and 34 for pM (LYM). Differences between pN1a and pN1bi and pN3 and pM (LYM) were significant (p < 0.05). In JBCS-NS, they were 87.8% and 968 for n0, 75.3% and 384 for n1α, 51.3% and 152 for n1β, 46.6% and 141 for n2, 21.2% and 33 for n3, 0% and 2 for n4d and n4i, respectively. Differences between n0 and n1α, n1α and n1β, and n2 and n3 were significant (p < 0.05). Conclusions With a large number of classification factors, UICC-NS was more complicated and hard to show significant difference in OS than JBCS-NS. But the latter also had redundant classifications. So, it is necessary to establish a new, simple, and easy-to-register node classification in future. J. Surg. Oncol. 2001;76:255–260. © 2001 Wiley-Liss, Inc.